Normally, the heart derives its energy by oxidative phosphorylation, in which each mole of glucose yields 36 mol of ATP. However, during hypoxia, glycolysis takes over, and 2 mol of ATP is provided by each mole of glucose; β-oxidation of fatty acids is also curtailed. If hypoxia is prolonged, cellular creatine phosphate and eventually ATP are depleted.
In ischemia, lactic acid accumulates and decreases intracellular pH. This condition inhibits glycolysis, fatty acid use, and protein synthesis, and therefore it results in cellular damage and eventually necrosis of myocardial cells.
1. The transmembrane action potentials recorded from cardiac myocytes may contain the following five phases: Phase 0: The action potential upstroke is initiated when a suprathreshold stimulus rapidly depolarizes the membrane by activating the fast sodium channels. Phase 1: The notch is an early partial repolarization that is achieved by the efflux of K+ through channels that conduct the transient outward current (ito). Phase 2: The plateau represents a balance between the influx of Ca++ through calcium channels and the efflux of K+ through several types of potassium channels. Phase 3: Final repolarization is initiated when the efflux of K+ exceeds the influx of Ca++ . The resultant partial repolarization rapidly increases K+ conductance and restores full repolarization.
Phase 4: The resting potential of the fully repolarized cell is determined by conductance of the cell membrane to K+ , mainly through iK1 channels.
2. Fast-response action potentials are recorded from atrial and ventricular myocardial fibers and from ventricular specialized conducting (Purkinje) fibers. Such an action potential is characterized by a large amplitude, a steep upstroke, and a relatively long plateau. The effective refractory period of fast-response fibers begins at the upstroke of the action potential and persists until midway through phase 3. The fiber is relatively refractory during the remainder of phase 3, and it regains full excitability soon after it is fully repolarized (phase 4).
3.
Slow-response action potentials are recorded from normal SA and AV nodal cells and from abnormal myocardial cells that have been partially depolarized. The action potential is characterized by a less negative resting potential, a smaller amplitude, a less steep upstroke, and a shorter plateau than is typical of the fast-response action potential. The upstroke in slow-response fibers is produced by the activation of calcium channels. Slow-response fibers become absolutely refractory at the beginning of the upstroke, and partial excitability may not be regained until very late in phase 3 or until after the fiber is fully repolarized.
4.
Normally, the SA node serves as the cardiac pacemaker to initiate the cardiac impulse. This impulse is propagated from the SA node to the atria and ultimately reaches the AV node. After a delay in the AV node, the cardiac impulse is propagated throughout the ventricles. Ectopic foci in the atrium, the AV node, or the His-Purkinje system may initiate propagated cardiac impulses if the normal pacemaker cells in the SA node are suppressed or if the rhythmicity of the ectopic automatic cells is abnormally enhanced.
5.
Under certain abnormal conditions, afterdepolarizations may be triggered by an otherwise normal action potential. EADs arise early in phase 3 of a normal action potential. They are more likely to occur when the basic cycle length of the initiating beats is very long and when the cardiac action potentials are abnormally prolonged. DADs appear late in phase 3 or in phase 4. They are more likely to occur when the basic cycle length of the initiating beats is short and when the cardiac cells are overloaded with Ca++ .
6.
Reentrant arrhythmias occur when a cardiac impulse traverses a loop of cardiac fibers and reenters previously excited tissue, when the impulse is conducted slowly around the loop, and when the impulse is blocked unidirectionally in some section of the loop.
7.